Estrogenic compounds and animal growth promoters



United States Patent 3,373,035 ESTROQENIC COMPOUNDS AND ANIMAL GROWTH PRDMUTERS Jerome L. Martin, Terre Haute, Ind, assignor to Conlmerciai Solvents Corporation, a corporation of Maryland No Drawing. Continuation-impart of application Ser. No. 561,400, June 29, 1966. This application Mar. 3, 1967, Ser. No. 620,284

6 Claims. (Cl. 99-2) ABSTRACT OF THE DlStJLQSURE where R is selected from the group consisting of hydrogen, lower alkyl and benzyl and animal feeds containing growth promoting amounts thereof.

This application is a continuation-impart of application Serial No. 561,400, filed June 29, 1966, now abandoned.

The present invention relates to new compounds and an object of the present invention is to provide compounds which exhibit estrogenic activity or aid in increasing the rate of growth in meat-producing animals, e.g. cattle, lamb and swine.

The compounds of this invention are illustrated by the formula:

where R is hydrogen, substituted or unsubstituted alkyl, e.g. lower alkyl such as methyl, ethyl, hexyl, etc. or aralkyl, e.g. benzyl.

The compounds of the present invention can be pro duced from the compound:

\CH=CH-(CH2)3 hereinafter referred to as the fermentation estrogenic substance (-F.E.S.) by direct fluorination in CCl F. The hydroxyl groups can be converted to ethers, e.g. methyl ethers, as taught in US. Patent 3,239,342. Benzyl ethers of F.E.S. are described in copending application Ser. No. 532,113, filed Mar. 7, 1966, now abandoned, and application Ser. No. 620,259, filed Mar. 3, 1967.

The compounds can be administered to animals by any suitable method including oral and parenteral administrations. For example, the compound can be blended with ordinary feed containing nutritional values in an amount suflicient to produce the desired rate of growth and can thus be fed directly to the animals, or the compound can be suspended in a suitable injection suspension medium such as peanut oil and injected parenterally. The amount of compound fed to an animal, of course, varies depending upon the animal, desired rate of growth and the like.

When the new compounds are to be administered in feeds, an animal feed composition may be prepared containing the usual nutritionally-balanced quantities of carbohydrates, proteins, vitamins and minerals, together with the compound of the present invention. Some of these usual dietary elements are grains, such as ground grain and grain by-products; animal protein substances, such as those found in fish meal and meat scraps, vegetable proteins like soybean oil meal or peanut oil meal; vitaminaceous materials, e.g. vitamin A and D mixtures; ribofiavin supplements and other vitamin B complex members; and bone meal and limestone to provide minerals. A type of conventional feed material for use with cattle includes alfalfa hay and ground corn cobs together with supplementary vitaminaceous substances if desired.

The following examples serve to illustrate the invention.

Example 1 RES. is fiuorinated directly by passing elemental fluorine into a solution of 32 grams F.E.S. dissolved in 400 grams of CCl F and held at -78 C. to produce i o=o noon-pn onaa The difiuoride is separated by evaporating the solvent CCigF followed by crystallization from methanol.

Example II F.E.S. 2,4-dimethylether, F.E.S.-4-benzyl ether, F.E.S.- 2,4-diethylether and F.E.S.-2-methylether are substituted for F.E.S. and the procedure of Example I is followed to produce the corresponding fluorinated F.E.S. compound.

Example Ill For young beef cattle, i.e., calves to yearlings running to two year olds, each animal is given 5 to 20 milligrams per day of the compound produced in Example I intimately admixed in about 18 to 22 pounds per head per day of a complete pelleted ration for about days. The complete pelleted ration includes in addition to the compound of Example I the following:

Barley "percent" 40-43 Molasses dried beet pulp do 34.537.5 Alfalfa pellets do 8.0 Tallow do 2.5 Calcium carbonate do .30 Urea do .30 Phosphorus source do .40 Salt do .50 Molasses do 10.00 Trace mineral do 0.5 Vitamin A MMl.U./ton 2-4 Note-Milo or corn, for example, can be substituted for the barley.

The compound of Example I is admixed with the above ingredients in a stationary blender or a feed mix truck in the following amounts in grams per ton to provide an 3 appropriate complete pelleted feed with dosage levels ranging from to 90 milligrams per head per day.

Grams/ton: Mg./head/day These gram amounts are premixed with, for example, 10 pounds of soybean hulls prior to admixture with the other ingredients.

Example V For young swine, i.e., six week old pigs to about 100 pound pigs, each animal is given 5 to 20 milligrams per day of the compound of Example I intimately admixed in about 1 /2 to 5 /2 pounds per head per day of a grower ration until it reaches a weight of about 100 pounds. When the swine weigh between 90 and 125 pounds the feed is changed to one whereby each animal is given 20 to 50 milligrams per day of the compound of Example I intimately admixed in about 5 /2 to 10 pounds per head per day of a finisher ration until it reaches market weight of about 220 pounds. The grower and finisher ration include in addition to the compound of Example I the following:

Grower, Finisher, percent percent Ground Yellow Corn 77 86. 7 Soybean Meal (44% protein) 16 6. 5 Meat and Bone Scraps (50% prote 2. 5 2. 5 Dehydrate Alfalfa Meal (17%) 2. 5 2. 5 Steamed Bone Meal 0. 5 0. 5 Ground Limestone O. 5 0.3 Iodized Salt a. 0. 5 0. 5 Vitamin, Antibiotic and Trace mix 0. 5 0.5

The compound of Example I is admixed with the above ingredients in a blender in the following amounts in milligrams per pound to provide an appropriate feed with dosage levels ranging from 6 to 96 milliagrams per head per day.

Mg./pound: Mg./head/day 2 6 4 12 S 24 16 48 32 96 Example VI For 4 to 10 month old lambs weighing 50 to 70 pounds, each animal is given 1 to milligrams per day of the compound of Example I, intimately admixed in about 3 to 6 pounds per head per day of a complete ration for 30 to 90 days. The complete ration includes in addition to the compound of Example I the following:

The compound of Example I is admixed with the above ingredients in a blender in the following amounts in milligrams per pound to provide an appropriate complete feed with dosage levels ranging from 1 to 15 milligrams per head per day.

Mg./pound: Mg./head/day .5 2

Example VII For broilers, i.e., day old to four week old chicks, a grower feed is prepared for feeding to the chicks for the first four weeks and a finisher feed is prepared for feeding the four week old chicks for the last five weeks until they reach market weight of two and a half to three pounds dressed. For each pound of weight gain, the chicks eat about 1.5 to 2 pounds of feed. Thus they eat about 1.5 pounds of feed during the first four weeks and about five pounds of feed during the next five weeks. During the course of this feeding schedule, each bird should receive a total of about 12 to 36 milligrams of the compound of Example I in the grower and finisher feed each of which includes in addition to the compound of Example I the following:

Grower Finisher Obs.) (lbs) Ground Yellow Corn 1, 000 1, 200 Soybean Meal (44% Protein) 700 500 Fish Meal Protein) 100 Alfalfa Meal 50 50 Meat and Bone Scraps 0 30 Animal Fat 80 80 Diealeium Phospha 35 40 Iodized Salt 1O 10 Limestone 15 Premix Vitamins Trace Minerals and Antibiotics 1O 10 It is claimed: 1.

No references cited.

A. LOUIS MONACELL, Primary Examiner.

H. H. KLARE, Assistant Examiner. 

